Project Summary Cochlear implants are neuroprosthetic devices that can provide hearing to deaf patients. However, the learning rates and peak performances of speech perception with cochlear implant use are highly variable across patient populations. Adaptation to use the electrical signals provided by cochlear implants is believed to require neuroplasticity within the central auditory system, and Individual differences in plasticity are thought to be an important source of outcome variability. However, the mechanisms by which behavioral training enables plasticity and improves outcomes are poorly understood. Here I propose investigate the hypothesis that neural mechanisms that promote plasticity in the rodent auditory system are key to optimizing cochlear implant usage, and might be especially helpful in cases of poor performance. In particular, we focus on noradrenergic modulation of the auditory thalamus and cortex by the locus coeruleus, which can enable robust and long- lasting neural and behavioral changes. When paired with sensory input, locus coeruleus stimulation leads to long-lasting improvements in auditory perception in normal-hearing animals that persist for at least weeks, and are due to changes occurring in both locus coeruleus and auditory cortex responses. Here we propose to apply this finding to the study of cochlear implant optimization by asking if locus coeruleus stimulation can also improve learning with cochlear implants. Recently we developed a new surgical approach for cochlear implantation in adult rats. Our approach optimizes insertion depth of a multi-channel electrode array (with eight separate channels) and allows animals to freely behave while using the cochlear implant to perform auditory-based behavioral tasks. Normal hearing rats are trained on an auditory recognition go/no-go task, and self-initiate trials to respond for a food reward to a target tone and withhold responses to non-target foil tones. Previously we have shown that this task requires auditory cortex activity, performance on the task affects auditory cortical responses to target and foil tones, and that this task is sensitive to cortical neuromodulation and receptive field plasticity. Thus we reasoned that cortical neuromodulation and plasticity might also be important for learning to recognize the behavioral meaning of cochlear implant stimulation. In this proposal, I will first monitor locus coeruleus noradrenergic neuron activity to determine when and how this system is activated during auditory and cochlear implant learning (Aim 1). Next I will ask if this system is necessary and sufficient for cochlear implant learning by reducing and increasing noradrenergic signaling during learning (Aim 2). Finally, I will record from the auditory cortex and thalamus of trained control cochlear- implanted animals and locus coeruleus modulated animals to determine how training and neuromodulation changes cortical and thalamic representations of the implant (Aim 3). The goal of these studies is to understand the critical role neuromodulation and neural plasticity play in cochlear implant outcomes.